The objective of this research is to develop novel 3D biodegradable porous polymer scaffolds with biomimetic extracellular matrix (ECM) coating for tissue engineering application. This SBIR Phase I proposal is to demonstrate the scaffold manufacturing feasibility by using a proprietary precision extruding deposition technique to fabricate porous 3D tissue scaffold with controlled porosity and internal architecture, and then coated the scaffold with a cell culture derived extracellular matrix (ECM) by using cell culture technology. We hypotheze that this cell culture derived biomimetic ECM coating, after proper decellularization and treatment, can offer similar biological performance as conventional tissue derived ECM in tissue engineering application. Toward this goal, we would like to demonstrate that an ECM coating can be generated onto the surface of porous tissue scaffolds. To achieve this aim, we first apply an enabling precision extruding deposition technique to freeformly fabricate porous 3D polycaprolactone (PCL) scaffolds with various porous structures. We then apply cell culture method to produce two types of ECM coatings using human dermal fibroblasts and human mesenchymal stem cells (under osteogeneic differentiation). We would like to further demonstrate that the decellularized biomimetic ECM coatings derived from two different cell lines (fibroblast and mesenchymal stem cells under osteogeneic differentiation) will affect osteo-differentiation of re-seeded mesenchymal stem cells. More specifically, we would like to demonstrate that the osteo- differentiated mesenchymal stem cells derived ECM coating could be used as a better ECM substrate for re-seeded mesenchymal stem cell in terms of the cell attachment, proliferation and differentiation down to the osteogeneic lineage. PUBLIC HEALTH RELEVANCE The project is aimed at developing novel 3D biodegradable porous polymer scaffolds with biomimetic extracellular matrix (ECM) coating for tissue engineering application. In this SBIR Phase I work, we will demonstrate the scaffold manufacturing feasibility by using a proprietary fabrication technique to produce porous 3D tissue scaffold with controlled porosity and internal architecture, and then use a cell culture technique to generate an extracellular matrix (ECM) as biomimetic coating. We believe that this novel manufacturing process will produce scaffolds with desired both biophysical properties and biological performance.